Genetic markers predict Alzheimer's risk

Three new genetic markers for Alzheimer's disease (AD) have been identified, pointing to a less well-known mechanism to explain how the disease develops.

The gene variants were uncovered by a team led by researchers from Washington University School of Medicine, USA, who linked biomarkers for AD to genes using information from over 1,200 people. The researchers measured amyloid-beta and tau proteins believed to be associated with AD found in the cerebrospinal fluid between the brain and the spine.

Amyloid-beta proteins, the focus of much of the current genetic research on AD, can stick together to form plaques outside neurons in the brain, while tau proteins tangle up inside the brain cells as the disease progresses. Both the plaques and tangles are prime suspects for the cell death and tissue loss that occurs in AD. After neurons die, their
contents end up in cerebrospinal fluid, which makes it possible for researchers
to measure them.

After comparing the genes of healthy elderly people with that of patients with AD, the team found that four gene variants were linked to high tau protein levels and a risk of AD, three of which were not previously known to be associated with the disease.

'We measured the tau protein in the cerebrospinal fluid and identified several genes that are related to high levels of tau and also affect risk for Alzheimer's disease', said Alison Goate, professor of genetics in psychiatry and co-author of the paper. 'As far as we're aware, three of these genes have no effect on amyloid-beta, suggesting that they are operating through a completely different pathway'.

The fourth gene the team found, APOE, is well known to the geneticists as it has been linked to AD before, but only via the amyloid-beta proteins. The new study found that APOE also affected levels of tau protein.

'It appears APOE influences risk in more than one way', said Professor Goate. 'Some of the effects are mediated through amyloid-beta and others by tau. That suggests there are at least two ways in which the gene can influence our risk for Alzheimer’s disease'.

The researchers explain that rising tau levels may predict the advancement of AD and the study may open up a new direction for drug development. 'Currently, there are a number of anti-amyloid-beta therapies in clinical trials, but it may be really helpful to have other drugs that target other components of the pathological cascade in Alzheimer's disease', Professor Goate told TIME.

Dr Doug Brown, director of research and development at the Alzheimer's Society, told the BBC that the identification of these new genetic markers may only represent a few of the many variants that may influence AD risk. 'It is important to stress that lifestyle factors also play a role, and research has shown that eating a balanced diet, exercising regularly, not smoking, and getting your blood pressure and cholesterol checked regularly are key ways to reduce your risk of dementia', he said.

The study was published in the journal Neuron.